Comment
that would require many years of an antiresorptive 5 Hansen S, Hauge EM, Beck Jensen JE, Brixen K. Differing effects of PTH 1-34,
drug treatment alone.16,17 In a direct comparator trial18
of romosozumab or alendronate for 1 year, followed by
alendronate for 2 years more in women with prevalent
vertebral fractures, the incidence of new vertebral
fractures was reduced by 37% at 1 year and 48% at
2 years in participants who received romosozumab
first, whereas the incidence of clinical and non-
vertebral fractures was significantly reduced in this
group compared with alendronate alone by the end of
the analysis (median 33 months).
Ultimately, these studies should lead clinicians to
reconsider the most efficient sequence of therapy in
patients at high risk of fracture: namely, a bone-forming
drug first, rather than one too late, or not at all.
Serge Livio Ferrari
Service and Laboratory of Bone Diseases, Geneva University
Hospital, 1205 Geneva, Switzerland
serge.ferrari@unige.ch
I have received grants for preclinical research with denosumab from AMGEN,
romosozumab from UCB, odanacatib from MSD, and consulting fees for clinical
trials development and interpretation from AMGEN, UCB, MSD, Radius,
and Agnovos.
1 Gehlbach S, Saag KG, Adachi JD, et al. Previous fractures at multiple sites
increase the risk for subsequent fractures: the Global Longitudinal Study of
Osteoporosis in Women. J Bone Miner Res 2012; 27: 645–53.
2 Yusuf AA, Matlon TJ, Grauer A, Barron R, Chandler D, Peng Y. Utilization of
osteoporosis medication after a fragility fracture among elderly Medicare
beneficiaries. Arch Osteoporos 2016; 11: 31.
3 Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of
pharmacologic treatments to prevent fractures: an updated systematic
review. Ann Intern Med 2014; 161: 711–23.
4 Dempster DW, Zhou H, Recker RR, et al. A longitudinal study of skeletal
histomorphometry at 6 and 24 months across four bone envelopes in
postmenopausal women with osteoporosis receiving teriparatide or
zoledronic acid in the SHOTZ trial. J Bone Miner Res 2016; 31: 1429–39.
Inclusion health: addressing the causes of the causes
Published Online The social gradient in health describes a graded
November 11, 2017
http://dx.doi.org/10.1016/
association between an individual’s position on
S0140-6736(17)32848-9 the social hierarchy and health: the lower the
See Articles page 241 socioeconomic position of an individual, the worse
See Review page 266
their health.1 The fact that the social gradient extends
from the highest echelons of society to the lowest
suggests that everyone is affected to a greater or
lesser extent by the social determinants of health.
One component of social cohesion is making
common cause between people at various points on
the social ladder. However, people at the extremes
can appear to be on a different scale to the rest of
186 www.thelancet.com Vol 391 January 20, 2018
PTH 1-84, and zoledronic acid on bone microarchitecture and estimated
strength in postmenopausal women with osteoporosis: an 18-month
open-labeled observational study using HR-pQCT. J Bone Miner Res 2013;
28: 736–45.
6 Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA.
Effects of teriparatide and alendronate on vertebral strength as assessed by
finite element modeling of QCT scans in women with osteoporosis.
J Bone Miner Res 2007; 22: 149–57.
7 Keaveny TM, McClung MR, Wan X, Kopperdahl DL, Mitlak BH, Krohn K.
Femoral strength in osteoporotic women treated with teriparatide or
alendronate. Bone 2012; 50: 165–70.
8 Hadji P, Zanchetta JR, Russo L, et al. The effect of teriparatide compared
with risedronate on reduction of back pain in postmenopausal women
with osteoporotic vertebral fractures. Osteoporos Int 2012; 23: 2141–50.
9 Gluer CC, Marin F, Ringe JD, et al. Comparative effects of teriparatide and
risedronate in glucocorticoid-induced osteoporosis in men: 18-month
results of the EuroGIOPs trial. J Bone Miner Res 2013; 28: 1355–68.
10 Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in
glucocorticoid-induced osteoporosis. N Engl J Med 2007; 357: 2028–39.
11 Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and
risedronate on new fractures in post-menopausal women with severe
osteoporosis (VERO): a multicentre, double-blind, double-dummy,
randomised controlled trial. Lancet 2017; published online Nov 9.
http://dx.doi.org/10.1016/S0140-6736(17)32137-2.
12 Miller PD, Delmas PD, Lindsay R, et al. Early responsiveness of women with
osteoporosis to teriparatide after therapy with alendronate or risedronate.
J Clin Endocrinol Metab 2008; 93: 3785–93.
13 Tsai JN, Uihlein AV, Burnett-Bowie SA, et al. Comparative effects of
teriparatide, denosumab, and combination therapy on peripheral
compartmental bone density, microarchitecture, and estimated strength:
the DATA-HRpQCT Study. J Bone Miner Res 2015; 30: 39–45.
14 Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on
new vertebral fractures in postmenopausal women with osteoporosis:
a randomized clinical trial. JAMA 2016; 316: 722–33.
15 Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin
monoclonal antibody) versus teriparatide in postmenopausal women
with osteoporosis transitioning from oral bisphosphonate therapy:
a randomised, open-label, phase 3 trial. Lancet 2017; 390: 1585–94.
16 Cosman F, Crittenden DB, Grauer A. Romosozumab treatment in
postmenopausal osteoporosis. N Engl J Med 2017; 376: 396–97.
17 Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment
in postmenopausal women with osteoporosis: results from the phase 3
randomised FREEDOM trial and open-label extension.
Lancet Diabetes Endocrinol 2017; 5: 513–23.
18 Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for
fracture prevention in women withosteoporosis. N Engl J Med 2017;
377: 1417–27.
society. F Scott Fitzgerald famously began his story
The Rich Boy, “Let me tell you about the very rich.
They are different from you and me”.2 In societies with
substantial inequality, the considerable gap between
the top 0·1% of income earners and the rest of society
threatens social cohesion.
Different, too, are socially excluded populations: the
homeless, people with substance use disorders, sex
workers, and prisoners. These individuals can seem
to be off the scale of the social hierarchy completely,
which represents a further challenge to social cohesion.
For example, in the first of two papers on inclusion

health in The Lancet, Robert Aldridge and colleagues3
found that socially excluded populations have a
mortality rate that is nearly eight times higher than
the average for men, and nearly 12 times higher for
women. By contrast, individuals (aged 15–64 years)
in the most deprived areas of England and Wales have
a mortality rate that is 2·8 times higher in men and
2·1 times higher in women than in individuals in the
least deprived areas. To adapt Jeremy Bentham’s turn
of phrase,4 social exclusion is deprivation upon stilts.
To put it less colourfully, the causes of excess morbidity
and mortality in socially excluded populations (ie, the
social determinants of health) are not so much different
from the causes of health inequalities more generally but
differ in their degree. Multiple intersecting causes and
multiple forms of morbidity characterise social exclusion.
The result is people with little hope or prospects and
considerably shortened lives. The challenge is to bring
socially excluded populations in from the cold—literally
and metaphorically—and to provide them with the
opportunity to be part of a diverse and flourishing
society. The concerned practitioner might despair at
achieving such social inclusion.
The second of the two papers on inclusion health in
The Lancet,by Serena Luchenski and colleagues,5 provides
evidence to banish despair. The authors report that
intervention is possible and can make a difference to the
lives of the four excluded groups included in their Review:
homeless individuals, prisoners, sex workers, and people
with substance use disorders. These four populations, of
course, overlap—eg, substance use disorder is common
in the other three socially excluded groups.
The methods used in both papers are of high quality.
But therein lies a problem. As identified by Luchenski
and coworkers, the effect of basing their work on
systematic reviews is a focus on proximate interventions
on individuals—eg, the Review includes many papers
on pharmacological treatment of substance use
disorder. These downstream interventions have been
covered, for the most part, in the scientific literature. There
has been much less focus on structural interventions. If
one went purely by the numbers of papers published,
one would put effort into pharmacological treatment
and would ignore housing; emphasise case management
and ignore poverty. Much of the literature included in
Luchenski and coworkers’ Review was from populations
with substance use disorders, with few publications about
www.thelancet.com Vol 391 January 20, 2018 187
Comment
Giacomo Pirozzi/Panos Pictures
homeless people and prisoners, and almost no studies on
sex workers. For individuals committed to evidence-based
policies, this poses a dilemma: efforts that promote social
inclusion have to be encouraged, but the fact that sex
workers have not been included in systematic reviews,
and prisoners have only been included rarely, should not
result in inaction.
The focus on systematic reviews of interventions
in Luchenski and colleagues’ Review is encouraging
because it means that much can be done, now and
relatively quickly, to promote inclusion health. Building
on the authors’ claim that structural interventions have
been underemphasised, the causes of the causes should
also be focused on.
A focus on the health of prisoners shows how a
societal approach must take different forms. Aldridge
and colleagues report that prisoners have shockingly
high all-cause mortality and mortality from injuries
and poisonings. Part of the reason will not be prison
itself but the multiple problems that prisoners have.
For example, prisoner’s involvement in drugs might
have resulted in their imprisonment. It is also well
known that exposure to adverse childhood experiences
increases the risk of substance use disorder, mental
illness, and violent behaviour—all of which increase
an individual’s risk of imprisonment.6 But, prison
might well be the worst place imaginable in which to
detain young people who are damaged. The public
need to be protected, of course, which is one reason
for imprisoning people,7 but by what stretch of the
imagination is it appropriate to detain young people
 Comment
with disordered behaviour, mental illnesses, or
multiple morbidities in a place that foments violence,
promotes drug use, and labels people for life, such
that their chances of being socially included on release
are drastically reduced? Deciding whether people are
damaged by prison or whether they brought all their
problems with them into prison is not straightforward.
On the assumption that prison does have negative
effects, then it is of concern that societies have markedly
different rates at which they imprison individuals.
In Japan, the prevalence of imprisonment is 48 per
100 000 individuals compared with 148 per 100 000 in the
UK and 698 per 100 000 in the USA.8 These differences, in
part, reflect differences in crime rates; but they also reflect
variation in the operation of the criminal justice system, in
policing practices, and the availability of guns.
A welcome feature of the inclusion health approach
advocated by Luchenski and colleagues5 is user involve­
ment, which aims to enable people to improve their own
health. We need the involvement of society as a whole
to tackle the causes of the causes of social exclusion and
its dramatic health consequences. This approach might
save money and it is the right thing to do.
The Lancet–CAMS Health Summit 2018: a call for abstracts
The Lancet and the Chinese Academy of Medical Sciences
(CAMS) have held three successful health summits in
2015–17 in Beijing, China. We continue to support China’s
health science research communities and invite abstract
188 www.thelancet.com Vol 391 January 20, 2018
Michael Marmot
UCL Institute of Health Equity, University College London,
London WC1E 6BT, UK
m.marmot@ucl.ac.uk
I declare no competing interests.
Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY 4.0 license.
1 Marmot M. The Health Gap. London: Bloomsbury; 2015.
2 F Scott Fitzgerald. The rich boy. New York: Scribner, 1926.
3 Aldridge RW, Story A, Hwang SW, et al. Morbidity and mortality in
homeless individuals, prisoners, sex workers, and individuals with
substance use disorders in high-income countries: a systematic review
and meta-analysis. Lancet 2017; published online Nov 11.
http://dx.doi.org/10.1016/S0140-6736(17)31869-X.
4 Schofield P. Jeremy Bentham’s ‘Nonsense upon Stilts’. 2013.
https://www.cambridge.org/core/services/aop-cambridge-core/content/
view/S0953820800003745 (accessed Oct 27, 2017).
5 Luchenski S, Maguire N, Aldridge RW, et al. What works in inclusion
health: overview of effective interventions for marginalised and excluded
populations. Lancet 2017; published online Nov 11.
http://dx.doi.org/10.1016/S0140-6736(17)31959-1 .
6 Bellis MA, Lowey H, Leckenby N, Hughes K, Harrison D. Adverse childhood
experiences: retrospective study to determine their impact on adult
health behaviours and health outcomes in a UK population. J Public Health
2014; 36: 81–91.
7 Nussbaum M. Anger and forgiveness: resentment, generosity, and justice.
New York: Oxford University Press; 2016.
8 Walmsley R. World prison population list. http://www.prisonstudies.org/
sites/default/files/resources/downloads/world_prison_population_
list_11th_edition_0.pdf (accessed Sept 22, 2017).
submissions from China for the 2018 The Lancet–CAMS
Health Summit, to be held on Oct 27–28 in Beijing.
Submissions are invited from all aspects of health science,
including, but not limited to: translational medicine;
clinical medicine; public health; global health; health
policy; the environment and ecological systems; primary
care; maternal, newborn, child, and adolescent health,
health professionalism; and medical education.
The event will consist of keynote presentations by
leading researchers from China and beyond, oral and
poster presentations of selected abstracts, launch of
The Lancet’s annual China themed issue, and writing and
publishing sessions with editors. The Lancet will publish
accepted abstracts online and in a conference booklet.
Abstracts must be relevant to health science in China.
The conference language will be English. Abstracts
should be written in English, up to 300 words in length,
with no references, tables, or figures. Submissions
should be structured and include the following sections:
background (including context and aim); methods;